POTASSIUM HOMEOSTASTASIS OF KV 1.3-DEFICIENT MICE

描述（改编自应用程序） 钾稳态的紊乱可导致致命的后果，如 心脏骤停肾脏是维持血清钾的重要器官 浓度在很窄的范围内。为了达到这个目的，肾上皮细胞 具有膜转运蛋白如Na-ATP酶和K通道。的 肾脏吸收和分泌钾的确切机制尚不完全 然而，最近的进展表明，钾通道可能起作用， 在这个过程中扮演重要角色。 除了内向整流钾通道外，电压门控钾通道也是 在肾脏中表达。加里·德西尔博士的实验室已经发现了几种 渠道其中两个已经被广泛表征：Kv1.3和KCNA 10。 尽管这些通道在肾K 内稳态尚不清楚，据推测，Kv1.3，与 ATP敏感性KATP通道，介导K退出进入钾离子， 返回到血流或积累和回收到细胞， Na+，K+-ATP酶泵。KCNA 10可能参与K运输， 血管张力、心脏动作电位和皮质醇分泌。 为了验证这些假设，我将研究Kv1.3的亚细胞定位 Kv1.3在肾上皮细胞中的表达，并使用 基因靶向本项目的具体目标是：（1）Kv1.3的本地化 在肾上皮细胞中。(2)Kv1.3缺陷小鼠的产生。（三） K0.3缺陷小鼠的表征。(4)KCNA 10敲除的产生 小鼠和Kv1.3/KCNA 10双敲除小鼠。

DESCRIPTION (adapted from the application) Disturbances of potassium homeostasis can result in fatal consequences such as cardiac arrest. The kidney is a vital organ that maintains serum potassium concentration in a very narrow range. To achieve this, renal epithelial cells are equipped with membrane transporters such as Na-ATPase and K channels. The exact mechanism of K absorption and secretion in the kidney is not completely understood, however, recent progress suggests that potassium channels may play an important role in the process. In addition to inward rectifier K channels, voltage-gated K channels are also expressed in kidney. Dr. Gary Desir's laboratory has identified several such channels. Two of these have been extensively characterized: Kv1.3 and KCNA10. Although the precise physiological role of these channels in renal K homeostasis is unclear, it is postulated that Kv1.3, in conjunction with ATP-sensitive KATP channels, mediates K exit into interstitium where K can be returned to blood stream or accumulated and recycled back into the cell by Na+,K+-ATPase pump. KCNA10 may participate in K transport, the regulation of vascular tone, the cardiac action potential, and cortisol secretion. To test these hypotheses, I will examine the sub-cellular localization of Kv1.3 in the renal epithelia, and study the Kv1.3 function in vivo using gene-targeting. The Specific Aims of the project are: (1) Localization of Kv1.3 in renal epithelial cells. (2) Generation of Kv1.3-deficient mice. (3) Characterization of the K0.3-deficient mice. (4) Generation of KCNA10 knockout mouse and Kv1.3/KCNA10 double knockout mouse.